學經歷

榮譽

指導學生獲獎

研究方向

隨著RNA沉默路徑的發現以及後轉錄調控的重要性逐漸被揭示，基因表達的調控已不再僅僅局限於轉錄層面，我們迎來了基因表達研究的新紀元。在這個嶄新的領域中，mRNA的加工、輸出、監控、沉默和降解等過程共同組成了一個精密的調控網絡，深刻影響著細胞和生物體的基因表達模式。

在mRNA的生命週期內，它以核糖核蛋白顆粒(mRNP)的形式存在，為眾多蛋白質的結合提供了理想平台，在後轉錄途徑的不同步驟中扮演著關鍵角色。令人驚奇的是，參與mRNA降解、監控、RNA沉默及轉譯抑制的蛋白質，經常共定位於mRNA處理體(P-body)中，顯示這些過程彼此緊密相連，而這些蛋白的異常會導致多種人類重要疾病，包括癌症和先天性免疫異常；然而，其詳細的調控機制卻知之甚少。

我們的研究目標是解開後轉錄層面調控機制的神秘面紗，並將這些發現應用於疾病治療中。通過細胞實驗與功能基因組學的結合，我們致力於揭示後轉錄過程之間的複雜關係及其對基因表達的深遠影響，深入理解它們與不同細胞進程間的聯繫，並鎖定內源性目標，從而闡明這些途徑受到干擾時所引發的複雜細胞和生物體表型。這些研究不僅僅增進了我們對基因表達調控的理解，更為許多重大疾病的治療提供了嶄新的思路。目前，我們正在探索如何針對特定的RNA結合蛋白開發新型抗癌機制，以及通過調控後轉錄途徑來抵禦病毒感染，希望能夠找到治療癌症和病毒感染的全新策略，為患者帶來新的希望。

研究著作

Chen TW, Liao HW, Noble M, Siao JY, Lo YT, Chang CT. (2024) Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions. eLife. (Reviewed Preprint)

Weber R, Chang CT. (2024) Human DDX6 regulates translation and decay of inefficiently translated mRNAs. eLife. 13:RP92426.

Chang CT. (2024) Analysis of Human Endogenous mRNA Deadenylation Complexes by High-Resolution Gel Electrophoresis. Methods Mol Biol. 2723:47-54.

Kao CY, Chang CT, Kuo PY, Lin CJ, Chiu HH, Liao HW. (2023) Sequential isolation of metabolites and lipids from a single sample to achieve multiomics by using TRIzol reagent.  Talanta. 258:124416. 

Enwerem III, Elrod ND, Chang CT, Lin A, Ji P, Bohn JA, Levdansky Y, Wagner EJ, Valkov E, Goldstrohm AC. (2021) Human Pumilio proteins directly bind the CCR4-NOT deadenylase complex to regulate the transcriptome. RNA. 27:445-464.

Arvola RM, Chang CT, Buytendorp JP, Levdansky Y, Valkov E, Freddolino PL, Goldstrohm AC. (2020) Unique repression domains of Pumilio utilize deadenylation and decapping factors to accelerate destruction of target mRNAs. Nucleic Acids Res. 48:1843-1871.

Hanet A, Räsch F, Weber R, Ruscica V, Fauser M, Raisch T, Kuzuoğlu-Öztürk D, Chang CT, Bhandari D, Igreja C, Wohlbold L. (2019) HELZ directly interacts with CCR4-NOT and causes decay of bound mRNAs. Life Sci Alliance. 2:e201900405.

Chang CT, Muthukumar S, Weber R, Levdansky Y, Chen Y, Bhandari D, Igreja C, Wohlbold L, Valkov E, Izaurralde E. (2019) A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5′-3′ messenger RNA decay. Nucleic Acids Res. [Epub ahead of print]

Raisch T*,Chang CT*, Levdansky Y*, Muthukumar S, Raunser S, Valkov E. (2019) Reconstitution of recombinant human CCR4-NOT reveals molecular insights into regulated deadenylation. Nat Commun. 10:3173. (*co-first)

Valkov E*, Muthukumar S*, Chang CT*, Jonas S, Weichenrieder O, Izaurralde E. (2016) Structure of the Dcp2-Dcp1 mRNA-decapping complex in the activated conformation. Nat Struct Mol Biol. 23:574-9. (*co-first)

Chen Y, Boland A, Kuzuoğlu-Öztürk D, Bawankar P, Loh B, Chang CT, Weichenrieder O, Izaurralde E. (2014) A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing. Mol Cell. 54:737-50.

Chang CT, Bercovich N, Loh B, Jonas S, Izaurralde E. (2014) The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1. Nucleic Acids Res. 42:5217-33.

Chang CT*, Hautbergue GM*, Walsh MJ, Viphakone N, van Dijk TB, Philipsen S, Wilson SA. (2013) Chtop is a component of the dynamic TREX mRNA export complex. EMBO J. 32:473-86. (*co-first)

Braun JE, Truffault V, Boland A, Huntzinger E, Chang CT, Haas G, Weichenrieder O, Coles M, Izaurralde E. (2012) A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5′ exonucleolytic degradation. Nat Struct Mol Biol. 19:1324-31.

Viphakone N, Hautbergue GM, Walsh M, Chang CT, Holland A, Folco EG, Reed R, Wilson SA. (2012) TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export. Nat Commun. 3:1006.

Cruz-Migoni A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang CT, Dickman MJ, Essex-Lopresti A, Harding SV, Mahadi NM, Marshall LE, Mobbs GW, Mohamed R, Nathan S, Ngugi SA, Ong C, Ooi WF, Partridge LJ, Phillips HL, Raih MF, Ruzheinikov S, Sarkar-Tyson M, Sedelnikova SE, Smither SJ, Tan P, Titball RW, Wilson SA, Rice DW. (2011) A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A. Science. 334:821-4.

Hautbergue GM, Hung ML, Walsh MJ, Snijders AP, Chang CT, Jones R, Ponting CP, Dickman MJ, Wilson SA. (2009) UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA. Curr Biol. 19:1918-24.

Su MC, Chang CT, Chu CH, Tsai CH, Chang KY. (2005) An atypical RNA pseudoknot stimulator and an upstream attenuation signal for -1 ribosomal frameshifting of SARS coronavirus. Nucleic Acids Res. 33:4265-75.